New potentiometric probes are proposed based on the concepts of electrochromism, charge-transfer, and thermochromism. Synthetic schemes and methodologies for the characterization of the probes are outlined. Several new strategies are described for the design of experiments aimed at measuring potential changes in single cells and in cells in suspension. These will allow the determination of rapid changes in cell suspensions and the detection of variations in single cells that are not triggered by a controlled external stimulus; currently, neither of these situations are generally accessible to the probe methodology. In addition, the temporal and spatial distribution of membrane potential induced by an external electric field on a variety of cells will be examined with the help of the potentiometric dyes. The following specific applications of these methodologies are proposed: 1) The place of the known membrane potential change within the cascade of biochemical and biophysical events accompanying the stimulus-response in neutrophils will be defined. 2) The kinetics for insertion of a variety of membrane permeabilizing agent into lipid vesicle and cell membranes will be characterized; among the agents to be examined is cytolysin, a cytotoxic factor derived from natural killer cells. 3) The possibility of an altered potential on the membrane of cells undergoing mitosis will be explored and correlated with other variations in cell surface properties. 4) Based on changing patterns of ion permeability during spermatogenesis, we will probe for expected variations of the potential along the mature sperm membrane.